1. Field of the Invention
This invention relates to sesquiterpene derivatives, and the pharmaceutically acceptable salts thereof, which have an inhibitory activity against the complement system of animals (an anticomplementary activity) and are useful as active ingredients in therapeutic compositions effective against autoimmune diseases, nephritis, rheumatism, collagen diseases, allergic diseases, etc., or as intermediates for producing such active ingredients.
2. Description of the Prior Art
The term "complement" refers to a complex group of proteins in body fluids that, working together with antibodies or other factors, play an important role as mediators of immune, allergic, immunochemical, and/or immunopathological reactions. Reactions in which a complement participates take place in blood serum or in other body fluids and hence are considered to be humoral reactions.
It has been reported that the complement system has been shown to be involved with inflammation, coagulation, fibrinolysis, antibody-antigen reactions and other metabolic processes (cf. U.S. Pat. No. 4,021,544, Bull. World Health Org., 39 935-938 (1968), Scientific American, 929 (No. 5) 54-66 (1973), Medical World News, October 11, 53-58, 64-66 (1974), Harvey Lectures, 66 75-104 (1972), The New England Journal of Medicine, 287 489-495, 545-549, 592-596, 642-646 (1972), The Johns Hopkins Med. J., 128 57-74 (1971), and Federation Proceedings, 32 134-137 (1973)).
Various compounds are known as compounds having an anticomplementary activity such as ethylenediamine tetraacetic acid (EDTA), Saldox, phlorizin (as described in Borsos. J. Immunol. 94 (4), 629 (1964)), hydroxybenzene derivatives (as described in Shir Mayer, Biochemistry N.Y., 7, 3003 (1968), guanidines and phenoxyacetamides (as disclosed in B. R. Baker, J. Med. Chem., 12, 408 (1968)), phosphonate esters (as disclosed in E. L. Becker, B.B.A., 147, 289 (1967)), chlorophyllin, glycyrrhizin, etc. However, these compounds are not satisfactory for practical purposes because they are highly toxic or they have a low anticomplementary activity. As far as is presently known, no anticomplementary compound or agent is commercially available.